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The Branched-Chain Amino Acid Transporter CD98 Heavy Chain Facilitates the Development of Colonic Macrophages Associated with Decreased Apoptosis in Macrophage Progenitors

ABSTRACT: The Branched-Chain Amino Acid Transporter CD98 Heavy Chain Facilitates the Development of Colonic Macrophages Associated with Decreased Apoptosis in Macrophage Progenitors

PROVIDER: PRJNA522426 | ENA |

REPOSITORIES: ENA

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Impact of Preoperative Oral Branched-chain Amino Acids on Reducing Postoperative Insulin Resistance.

Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery. There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.

| 2744698 | ecrin-mdr-crc

Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

Project description:Branched‐chain amino acid (BCAA) metabolism is a central hub for energy production and regulation of numerous physiological processes. Controversially, both increased and decreased levels of BCAAs are associated with longevity. Using genetics and multi‐omics analyses in Caenorhabditis elegans, we identified adaptive regulation of the ubiquitin‐proteasome system (UPS) in response to defective BCAA catabolic reactions after the initial transamination step. Worms with impaired BCAA metabolism show a slower turnover of a GFP‐based proteasome substrate, which is suppressed by loss‐of‐function of the first BCAA catabolic enzyme, the branched‐chain aminotransferase BCAT‐1. The exogenous supply of BCAA‐derived carboxylic acids, which are known to accumulate in the body fluid of patients with BCAA metabolic disorders, is sufficient to regulate the UPS. The link between BCAA intermediates and UPS function presented here sheds light on the unexplained role of BCAAs in the aging process and opens future possibilities for therapeutic interventions.

2022-09-22 | GSE185451 | GEO

The Branched-Chain Amino Acid Transporter CD98 Heavy Chain Facilitates the Development of Colonic Macrophages Associated with Decreased Apoptosis in Macrophage Progenitors

Project description:We performed a single-cell transcriptome analysis of colon monocytes and macrophages from corn oil treated CD98ΔCX3CR1 mice and tamoxifen induced conditional Cd98 KO (CD98ΔCX3CR1) mice.

2020-01-21 | GSE126574 | GEO

Nervous system reduction in branched-chain amino acid metabolism disrupts hippocampal neurogenesis and memory

Project description:To study the role of branched-chain amino acid metabolism in neural stem cells we generated two primary neural stem cell culture lines in which on was deleted for the Ppm1k gene using floxed cells and adenovirus delviered cre-recombinase.

2023-04-06 | GSE205603 | GEO

Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan

Project description:Development, growth and adult survival are coordinated with available metabolic resources. The insulin/IGF and TOR signaling pathways relay nutritional status, thereby ascertaining that the organism responds appropriately to environmental conditions. MicroRNAs are short (21-23 nt) regulatory RNAs that confer specificity on the RNA-induced silencing complex (RISC) to inhibit a given set of mRNA targets. We profiled changes in miRNA expression during adult life in Drosophila melanogaster and determined that miR-277 is down-regulated with age. This miRNA controls branched-chain amino acid (BCAA) catabolism and the activity of the TOR kinase, a central growth regulator. Metabolite analysis suggests that the mechanistic basis may be an accumulation of BCKAs, rather than BCAAs, thus avoiding potentially detrimental consequences of increased branched chain amino acid levels on e.g. translational fidelity. Constitutive miR-277 expression as well as transgenic inhibition with a miRNA sponge construct shortens lifespan. Furthermore, constitutive miR-277 expression is synthetically lethal with reduced insulin signaling. Thus, optimal metabolic adaptation requires tuning of cellular BCAA catabolism by miR-277 to be concordant with systemic growth signaling.

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Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

Project description:Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

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Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

Project description:Branched chain amino acids (BCAAs) play an important role in energy and protein regulation. Defects in BCAA metabolism are linked to numerous pathologies, including diabetes, neurodegeneration, and premature aging. Isovaleric acidemia is a metabolic disease caused by defective leucine breakdown and an abnormal accumulation of isovaleric acid in the body fluids; however, the cytotoxic effects caused by excess isovaleric acid remained unclear. Here, we provide a regulatory connection between BCAA metabolism and the ubiquitin/proteasome-system (UPS) in Caenorhabditis elegans. Multi-omic analysis identified that worms lacking the isovaleryl-CoA dehydrogenase IVD-1 exhibit reduced expression of regulatory proteasome subunits and defects in ubiquitin-dependent proteolysis. Conversely, proteasomal protein degradation was supported by the branched chain amino transferase BCAT-1. Adding extra isovaleric acid to the growth medium triggered UPS defects, implying a causative role of perturbed proteostasis in isovaleric academia.

2022-09-22 | PXD028286 | Pride

A new form of Staphylococcus aureus dormancy controlled by branched-chain amino acid availability in human macrophages

Project description:Staphylococcus aureus is a human commensal bacterium and opportunistic pathogen. Chronicity of S. aureus infection has been linked to bacterial survival within host cells including macrophages. Bacteria recovered from the intracellular milieu often form small colony variants (SCV) which are growing slowly, show reduced virulence factor production and are more resistant to antibiotics. Branched chain amino acids (BCAA) are an important class of nutrients for S. aureus. We therefore tested if components of BCAA biosynthesis or transport would alter the outcome of macrophage infection. We found that S. aureus mutants in the BCAA transporter BrnQ1 survived experimental infection of primary human macrophages for the complete duration of the 28 day experiments. Since phenotypic differences between brnQ1 mutants and wild-type bacteria occurred around 10 h p.i., we performed dual RNA-seq by which we determined the transcriptomes of both, pathogen and macrophage host, simultaneously. Our data indicate that at that time transcriptomic changes exclusively are governed by the internalized pathogen. The differential analysis of S. aureus WT and its isogenic brnQ1 mutant surprisingly demonstrated a dysregulation of iron-dependently regulated genes.

2023-06-28 | GSE235929 | GEO

The Effect of Branched Chain Amino Acid to the Perioperative Nutritional Status: In Patients with Cirrhosis Undergoing Liver Resection and Patients Awaiting Liver Transplantation.

Project description:Interventions: Patients assigned for intervention group take Branched-chain amino acid formula as late-evening snack for 2 weeks preoperatively in hepatic resction,and for 4 weeks in liver transplantation,respectively. Administration of BCAA formula would be maintained for 12 weeks postoperatively in both procedure. Patients in the control group are observed without administration of BCAA formula. Primary outcome(s): Body cell mass Study Design: Parallel Non-randomized

| 2624553 | ecrin-mdr-crc

Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control

Project description:Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets led to hyperphagia, obesity and reduced lifespan. These effects were not due to elevated BCAA per se or hepatic mTOR activation, but rather the shift in balance between dietary BCAAs and other AAs, notably tryptophan and threonine. Increasing the ratio of BCAAs to these AAs resulted in hyperphagia and was linked to central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averted the health costs of a high BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes were not due to intrinsic toxicity; rather, to hyperphagia driven by AA imbalance.

2019-03-11 | GSE114855 | GEO

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